Porphyrin Ligand Research Articles

Assessment of polyfunctional macrocyclic compounds in solution by cryoscopic method

The article considers the synthesis of meso-tetrakis(1'-methyl-pyrid-4-yl)porphyrin tetratosylate and meso-tetrakis(1'-methyl-carboxymethylpyrid-4-yl)porphyrin tetrabromide. The authors qualified the porphyrin ligands in terms of the electron and 1H NMR spectroscopy. The research determines the decrease of freezing point (ΔTfr) of aqueous solutions of porphyrins, as well as a model N-methyl-pyridinium salt (1 methyl-pyridinium iodide). We used the obtained experimental values of ΔT3 to determine the isotonic coefficient. The obtained results indicate the compounds are almost completely dissociated in the indicated concentration range in dilute solutions.

An Insight on the Potential of Manganese Porphyrins in Cancer Treatment

Abstract: Porphyrin ligands are recognized for their exclusive tendency to form metal porphyrin complexes of pronounced value. Such metal porphyrin complexes display their inimitable roles as catalysts in various fields viz. conversion reactions, oxidation reactions, organic synthesis, pharmaceutical areas, biological and environmental fields, and many more. Out of different metal porphyrins; manganese porphyrins are one of the appreciated metal porphyrins due to their prodigious catalytic performance and potential in cancer treatment. In this perspective, the proficient participation of manganese porphyrins in the treatment of cancer along with operative discussions on molecular pathways have been briefly but effectively assessed based on the recent scientific literatures available.

Use of Single-Molecule Plasmon-Enhanced Fluorescence to Investigate Ligand Binding to G-Quadruplex DNA.

Single-molecule measurements are crucial for studying the interactions between G-quadruplex (GQ) DNA and ligands, as they provide higher resolution and sensitivity compared to those of bulk measurements. In this study, we employed plasmon-enhanced fluorescence to investigate the real-time interaction between the cationic porphyrin ligand TmPyP4 and different topologies of telomeric GQ DNA at the single-molecule level. By analyzing the time traces of the fluorescence bursts, we extracted dwell times for the ligand. For parallel telomeric GQ DNA, the dwell time distribution followed a biexponential fit, yielding mean dwell times of 5.6 and 18.6 ms. For the antiparallel topology of human telomeric GQ DNA, plasmon-enhanced fluorescence of TmPyP4 was observed, with dwell time distributions following a single-exponential fit and a mean dwell time of 5.9 ms. Our approach allows the nuances of GQ-ligand interactions to be captured and holds promise for studying weakly emitting GQ ligands at the single-molecule level.

The construction of Fe-porphyrin nanozymes with peroxidase-like activity for colorimetric detection of glucose

As a type of nanomaterials with enzyme-mimetic catalytic properties, nanozymes have attracted wide concern in biological detection. H2O2 was the characteristic product of diverse biological reactions, and the quantitative analysis for H2O2 was an important way to detect disease biomarkers, such as acetylcholine, cholesterol, uric acid and glucose. Therefore, there is of great significance for developing a simple and sensitive nanozyme to detect H2O2 and disease biomarkers by combining with corresponding enzyme. In this work, Fe-TCPP MOFs were successfully prepared by the coordination between iron ions and porphyrin ligands (TCPP). In addition, the peroxidase (POD) activity of Fe-TCPP was proved, in detail, Fe-TCPP could catalyze H2O2 to produce ·OH. Herein, glucose oxidase (GOx) was chosen as the model to build cascade reaction by combining Fe-TCPP to detect glucose. The results indicated glucose could be detected by this cascade system selectively and sensitively, and the limit of detection of glucose was achieved to 0.12 μM. Furthermore, a portable hydrogel (Fe-TCPP@GEL) was further established, which encapsulated Fe-TCPP MOFs, GOx and TMB in one system. This functional hydrogel could be applied for colorimetric detection of glucose by coupling with a smartphone easily.

Hydrocarbon Oxidation by a Porphyrin‐π‐Cation Radical Complex

AbstractHeme and chlorin π‐cation radical oxidants are widely implicated in biological and synthetic oxidation catalysis. Little insight into the role of π‐cation radicals in proton coupled electron transfer (PCET) oxidation is available. We prepared a NiII‐porphyrin‐π‐cation complex ([NiII(P⋅+)]) and found it to be capable of the oxidation of a variety of simple hydrocarbon substrates. Interestingly, some of the products were hydroxylated, with ([NiII(P⋅+)]) working in concert with atmospheric O2 to yield hydroxylated hydrocarbons. Kinetic data suggested that the porphyrin‐π‐cation radical species oxidised substrates through a concerted PCET mechanism, where the porphyrin‐π‐cation radical accepted the electron, and the proton was transferred to a free anion. Our findings highlight the potential role of π‐cation radicals as hydrocarbon activators, demonstrating that porphyrin ligand non‐innocence could be a readily manipulated resource for oxidation catalyst development.

Hydrocarbon Oxidation by a Porphyrin-π-Cation Radical Complex.

Heme and chlorin π-cation radical oxidants are widely implicated in biological and synthetic oxidation catalysis. Little insight into the role of π-cation radicals in proton coupled electron transfer (PCET) oxidation is available. We prepared a NiII-porphyrin-π-cation complex ([NiII(P•+)]) and found it to be capable of the oxidation of a variety of simple hydrocarbon substrates. Interestingly, some of the products were hydroxylated, with ([NiII(P•+)]) working in concert with atmospheric O2 to yield hydroxylated hydrocarbons. Kinetic data suggested that the porphyrin-π-cation radical species oxidised substrates via a concerted PCET mechanism, where the nickel porphyrin-π-cation radical accepted the electron, and the proton was transferred to a free anion. Our findings highlight the potential role of π-cation radicals as hydrocarbon activators, demonstrating that porphyrin ligand non-innocence could be a readily manipulated resource for oxidation catalyst development.

Second-sphere tuning of analogues for the ferric-hydroperoxoheme form of Mycobacterium tuberculosis MhuD

Mycobacterium tuberculosis MhuD catalyzes the oxygenation of heme to mycobilin; experimental data presented here elucidates the novel hydroxylation reaction catalyzed by this enzyme. Analogues for the critical ferric–hydroperoxoheme (MhuD–heme–OOH) intermediate of this enzyme were characterized using UV/Vis absorption (Abs), circular dichroism (CD), and magnetic CD (MCD) spectroscopies. In order to extract electronic transition energies from these spectroscopic data, a novel global fitting model was developed for analysis of UV/Vis Abs, CD, and MCD data. A variant of MhuD was prepared, N7S, which weakens the affinity of heme-bound enzyme for a hydroperoxo analogue, azide, without significantly altering the protein secondary structure. Global fitting of spectroscopic data acquired in this study revealed that the second-sphere N7S substitution perturbs the electronic structure of two analogues for MhuD–heme–OOH: azide-inhibited MhuD (MhuD–heme–N3) and cyanide-inhibited MhuD (MhuD–heme–CN). The ground state electronic structures of MhuD–heme–N3 and MhuD–heme–CN were assessed using variable-temperature, variable-field MCD. Altogether, these data strongly suggest that there is a hydrogen bond between the Asn7 side-chain and the terminal oxygen of the hydroperoxo ligand in MhuD–heme–OOH. As discussed herein, this finding supports a novel hydroxylation reaction mechanism where the Asn7 side-chain guides a transient hydroxyl radical derived from homolysis of the OO bond in MhuD–heme–OOH to the β- or δ-meso carbon of the porphyrin ligand yielding β- or δ-meso-hydroxyheme, respectively.

Two-dimensional iron porphyrin nanozyme mimics cytochrome P450 activity for cancer proliferation inhibition

Two-dimensional materials have excellent performance in energy catalysis and biomedicine due to their unique advantages in surface and interfacial properties. Taking into account the unique advantages of the surface interface and catalysis of two-dimensional materials, it is a very feasible way to construct two-dimensional materials with clear atomic structure to break the redox balance in tumor cells, so as to achieve efficient anti-tumor effects. Based on this, we selected the porphyrin ligands that widely exist in nature, equipped with iron metal active centers, and constructed a two-dimensional iron porphyrin nanozyme with a clear atomic structure, which simulated the redox activity of cytochrome P450 enzymes. The experimental results show that by carrying a rotatable pyridine group on the porphyrin ring, the iron porphyrin monomers can be effectively connected and expanded into a two-dimensional iron porphyrin microstructure. Enough iron centers are exposed on the surface of two-dimensional iron porphyrins as catalytic sites. In the presence of oxidants, two-dimensional iron porphyrins can efficiently catalyze the oxidation of small organic molecules, and have good P450-like enzymatic activity. At the same time, the two-dimensional iron porphyrin nanomaterial was used for anti-tumor, and it was found that it has an efficient ability to inhibit tumor proliferation, which may be due to the catalytic oxidation of various organic small molecules in tumor cells by the high concentration of hydrogen peroxide in tumor cells. At the same time, we found that the two-dimensional iron porphyrin nanozyme may have a good drug loading capacity due to the many exposed iron sites on its surface, which provides a possible option for drug loading to achieve combined high-efficiency tumor therapy.

Engineered MOF-Enzyme Nanocomposites for Tumor Microenvironment-Activated Photodynamic Therapy with Self-Luminescence and Oxygen Self-Supply

Photodynamic therapy (PDT) is a promising strategy for cancer treatment. However, its efficiency is hindered by three key parameters, namely, limited penetration depth of external light, tumor hypoxia, and self-aggregation of photosensitizers. Herein, we fabricated a novel "all-in-one" chemiluminescence-PDT nanosystem through the integration of an oxygen-supplying protein (hemoglobin, Hb) and a luminescent donor (luminol, Lum) in hierarchically engineered mesoporous porphyrinic metal-organic framework (MOF) nanoparticles. Mechanistically, the in situ chemiluminescence of Lum is activated by the high concentration of H2O2 in 4T1 cancer cells and further catalyzed by Hb and then absorbed by the porphyrin ligands in MOF nanoparticles through chemiluminescence resonance energy transfer. The excited porphyrins then sensitize oxygen supplied by Hb to produce sufficient reactive oxygen species that kill cancer cells. The MOF-based nanocomposite demonstrates excellent anticancer activity both in vitro and in vivo, with eventually a 68.1% tumor inhibition rate after intravenous injections without external light irradiation. This self-illuminating, oxygen-self-supplying nanosystem integrates all essential components of PDT into one simple nanoplatform, demonstrating great potential for the selective phototherapy of deep-seated cancer.

Water-Soluble Gd(III)-Porphyrin Complexes Capable of Both Photosensitization and Relaxation Enhancement.

With the aim of developing more stable Gd(III)-porphyrin complexes, two types of ligands 1 and 2 with carboxylic acid anchors were synthesized. Due to the N-substituted pyridyl cation attached to the porphyrin core, these porphyrin ligands were highly water-soluble and formed the corresponding Gd(III) chelates, Gd-1 and Gd-2. Gd-1 was sufficiently stable in neutral buffer, presumably due to the preferred conformation of the carboxylate-terminated anchors connected to nitrogen in the meta position of the pyridyl group helping to stabilize Gd(III) complexation by the porphyrin center. 1H NMRD (nuclear magnetic relaxation dispersion) measurements on Gd-1 revealed high longitudinal water proton relaxivity (r1 = 21.2 mM-1 s-1 at 60 MHz and 25 °C), which originates from slow rotational motion resulting from aggregation in aqueous solution. Under visible light irradiation, Gd-1 showed extensive photoinduced DNA cleavage in line with efficient photoinduced singlet oxygen generation. Cell-based assays revealed no significant dark cytotoxicity of Gd-1, while it showed sufficient photocytotoxicity on cancer cell lines under visible light irradiation. These results indicate the potential of this Gd(III)-porphyrin complex (Gd-1) as a core for the development of bifunctional systems acting as an efficient photodynamic therapy photosensitizer (PDT-PS) with magnetic resonance imaging (MRI) detection capabilities.

Preparation of CO2‐based poly(carbonate‐co‐lactide) with different porphyrin aluminum (III) catalysts

AbstractTwo‐component catalysts composed of tetra (para‐X substituted) phenylporphyrin aluminum (III) chloride, T (p‐X‐P)PAlCl, (where X = H, F, Cl, Br, CH3, OCH3, tert‐butyl), and cocatalyst bis(triphenylphosphine)imminium chloride (PPN+Cl−), could initiate the polymerization of propylene oxide (PO). And they could react with rac‐lactide, (rac‐LA), in the presence of propylene oxide (PO), to yield chains of enriched isotactic polylactide (PLA) with trace polyether segment. Also, these catalysts displayed different catalytic activity in the copolymerization of CO2 and PO, resulting in poly(carbonate‐co‐ether) copolymer with different carbonate unit content (CU%). Further, these catalysts could initiate one‐pot regio‐ and stereo‐ selective terpolymerization of rac‐LA, CO2 and rac‐PO, resulting in multi‐blocky poly(carbonate‐co‐lactide) with trace polyether segment. The structure of the products was verified by 1H NMR, 13C NMR, GPC, and DSC analysis, and it was found that variation of substitution groups in the periphery of porphyrin ligand would affect on the catalytic efficiency of ter‐polymerization, and the relative polymerization reaction ratio of the ring‐opening polymerization of LA (ROP) to the ring‐opening copolymerization of PO and CO2 (ROCOP), resulting in ter‐polymer with different contents of PLA segment and PPC segment. However, H‐T% in polycarbonate unit and Pi% in polylactide unit did not vary much with the change of catalysts.

Highly efficient visible-light photocatalytic nitrogen fixation via single-atom iron catalyst site and synergistic effect of Zr-cluster in zirconium-based porphyrinic metal-organic frameworks (PCN-222)

Zirconium-based porphyrinic metal-organic frameworks (MOFs), including PCN-222 (nonmetal), and PCN-222 (Fe) were employed as the photocatalyst for photocatalytic nitrogen (N2) fixation to NH3 under visible light irradiation. The as-synthesized MOFs of PCN-222 (nonmetal) and PCN-222 (Fe) exhibited a notable increase in photocatalytic N2 fixation compared to the pure (Metallo) porphyrin ligands of H2TCPP and FeTCPP, respectively. The comparative studies illustrated that using the Zr-cluster as a stable node and the active redox site is a successful strategy to increase the stability and photocatalytic activity of the MOF-based photocatalysts. On the other, the single-atom Fe site as an active center of absorption and activation of nitrogen molecules improved the N2 fixation activity. Remarkably, among them all, PCN-222 (Fe) demonstrated the highest photocatalytic N2 fixation activity with a rate of 1502.51 μmol g-1h−1 which could be related to the simultaneous presence of Zr-cluster and single-atom Fe site which promote the performance of the photocatalyst. So, the photocatalytic activity of PCN-222 (Fe) is 1.9 and 2.5 times higher than the activity of PCN-222 (nonmetal) and pure FeTCPP, respectively. High photocatalytic activity, sacrificial agent-free conditions, excellent efficiency in short response time, reusability, and mild reaction conditions are the attractive characteristics of the as-synthesized photocatalysts that make them suitable candidates for photocatalytic NH3 production.

Ratiometric Fluorescence Assay for Pyrophosphate Based on Sulfur Nanodots Decorated Metal-Organic Frameworks.

Selective and sensitive detection of inorganic pyrophosphate (PPi) are of great significance both for clinical applications and fundamental research. In this work, a ratiometric fluorescent probe was developed by decorating a porphyrin-based metal-organic framework (PCN-224) with sulfur nanodots (S-dots). The red-fluorescence of PCN-224 was significantly promoted (more than 6-fold) by S-dots through inhibiting molecular motion of porphyrin ligand, which also provided active sites for the detection of Cu2+ and PPi. Cu2+ could selectively quench the red-fluorescence of PCN-224 through coordination with porphyrin ligand, and the competition reaction between PPi and Cu2+ resulted in the decomposing of coordination and recovery of red-fluorescence. The blue-fluorescence from S-dots was deemed as effective reference, which provided a built-in correction in complex environments. Based on these photophysical properties, a ratiometric fluorescence assay was developed for the quantitative detection of Cu2+ and PPi, with a limit of detection of 0.11 and 2.66 μM, respectively. The accuracy and practical applications of assays were also demonstrated by detection in tap water and human serum samples.

Spectrophotometric study of basic properties of glycosylated tetraphenylporphin derivatives

The paper presents the results of spectrophotometric study of the basic properties of glycosylated substituted derivatives of 5,10,15,20-tetraphenylporphyrin, namely 5-(4′- O -galactosylphenyl)-10,15,20-tris( N -methylpyridin-3-yl)porphine, 5,15-bis(4′- O -galactosylphenyl)-10,20-bis( N -methylpyridin-3-yl)porphine, 5,10,15,20-tetra( N -methylpyridin-3-yl)porphin, 5,10,15,20-tetra(4- O -galactosylphenyl)porphin. The basic properties of the studied ligands in acetonitrile at 298 K were studied by spectrophotometric method. The effect of glycosylated fragments, as constituents of a macromolecule, on protolytic equilibria during acid-base interactions of the ligand in basic media and the change in the reactivity of porphyrin ligands depending on the nature of the peripheral substituent was analyzed.

Donor–Acceptor Mixed-Naphthalene Diimide-Porphyrin MOF for Boosting Photocatalytic Oxidative Coupling of Amines

Integrating electron donor and acceptor chromophores as ligands within one MOF for light harvesting and photocatalysis appears to be a major synthesis challenge. Meanwhile, high-efficiency and selective aerobic oxidative coupling of amines to imines under mild conditions is highly desirable for scientific and industrial fields. Herein, via a facile one-pot synthetic strategy, an electron donor porphyrin ligand 5,15-di(p-benzoato)porphyrin (H2DPBP) was successfully integrated into a naphthalene diimide (electron acceptor)-based Zr-MOF (Zr-NDI) to construct a mixed-ligand MOF (Zr-NDI-H2DPBP) benefiting from the two ligands with similar geometry and connectivity. When utilized as a heterogeneous photocatalyst for aerobic oxidative coupling of benzylamine at room temperature, the prepared mixed-ligand Zr-NDI-H2DPBP exhibited a boosted imine generation rate (136 mmol g–1 h–1) far exceeding those of other noble-metal-free MOF photocatalysts and can be successfully applied to various benzylamine derivatives. Furthermore, from the results of the experiments and density functional theory calculations, the photocatalytic performance of Zr-NDI-H2DPBP is attributed to the photoinduced electron transfer from the donor H2DPBP to the acceptor NDI and the energy transfer facilitated by the photosensitized H2DPBP under irradiation, which effectively improve the electron–hole separation efficiency to generate abundant reactive active species of superoxide radical (O2•–) and singlet oxygen (1O2), respectively. This work provides an avenue to construct electron donor and acceptor chromophore-based light-harvesting systems by utilizing mixed-ligand MOFs as platforms to boost the solar-energy conversion.

Investigating the sensitization of the ytterbium(III) NIR emission by non-sandwich type Yb(III)-porphyrin coordination compounds

Two porphyrin ligands with peripheral chelate groups linked at meso and β positions and their two new non-sandwich-type ytterbium(III)-porphyrin coordination compounds have been synthesized. New porphyrin compounds and the two coordination compounds were characterized by Nuclear Magnetic Resonance, High Resolution Mass Spectrum, Ultraviolet and visible, and fluorescence in the visible and Near Infrared (NIR) regions. The two Yb(III) complexes afforded the photoluminescence quantum yields of 2.0% and 1.6% for Yb(III) characteristic NIR emission in DMSO. Finally and importantly, the impact factors on the sensitization of Yb(III) NIR emission by porphyrin ligands via non-sandwich-type linkage were investigated by theoretical calculations and further measurements on fluorescent properties. It is proposed that the sensitization efficiency for the distance between the sensitizer and Yb(III) NIR emitter is better than that for conjugated degree of the peripheral porphyrin linkage.

Spectating the proton migration on catalyst with noninnocent ligand in aqueous electrochemical CO2 reduction

It is of great significance to investigate aqueous CO2 reduction on catalysts with redox-noninnocent ligands as they effectively facilitate CO2 reduction but circumvent the H2 evolution. By developing the methodology of rapid-scan FT-IR in external reflection mode, the pathway of CO2 reduction on iron porphyrin was in-situ monitored. It’s uncovered that coupled with first-electron reduction of [FeIITAPP]0, the porphyrin nitrogen is protonated as the observation of NH+ ammonium band in IR spectra, which avoids the formation of Fe–H structure for proton reduction. Moreover, an inverse kinetic isotope effect (KIE = 0.59) in formation of *COOH indicates the protonated porphyrin-N would also act as a proton relay for the efficient inner-sphere proton transfer to the activated CO2 molecules. This work experimentally identified the proton migration pathway via the reduced porphyrin ligand as proton shuttle for the first time and should benefit the design of the catalyst of high CO2 reduction selectivity.

Nanoscale Two-Dimensional FeII- and CoII-Based Metal-Organic Frameworks of Porphyrin Ligand for the Photodynamic Therapy of Breast Cancer.

The delivery of biocompatible reagents into cancer cells can elicit an anticancer effect by taking advantage of the unique characteristics of the tumor microenvironment (TME). In this work, we report that nanoscale two-dimensional FeII- and CoII-based metal-organic frameworks (NMOFs) of porphyrin ligand meso-tetrakis (6-(hydroxymethyl) pyridin-3-yl) porphyrin (THPP) can catalyze the generation of hydroxyl radicals (•OH) and O2 in the presence of H2O2 that is overexpressed in the TME. Photodynamic therapy consumes the generated O2 to produce a singlet oxygen (1O2). Both •OH and 1O2 are reactive oxygen species (ROS) that inhibit cancer cell proliferation. The FeII- and CoII-based NMOFs were non-toxic in the dark but cytotoxic when irradiated with 660 nm light. This preliminary work points to the potential of porphyrin-based ligands of transition metals as anticancer drugs by synergizing different therapeutic modalities.

Dimension-driven cobalt porphyrin nanoframework mimics dehydrogenase activity for inhibition of cancer proliferation

Dehydrogenases are a class of oxidoreductases that catalyze a wide variety of oxidative reactions in living organisms to maintain the redox homeostasis. Developing materials with dehydrogenase activity to break the homeostasis for the treatment of diseases with immortal proliferative properties has broad application prospects. Here, we use porphyrin ligands with good biocompatibility, and Co metal centers with high catalytic activity to jointly construct various dimensional Co porphyrin nano-coordination frameworks, and mimicking their catalytic performance of dehydrogenase activity. The results show that the one-dimensional nanoframeworks have the best dehydrogenase-like catalytic oxidation efficiency. At the same time, the cobalt porphyrin nanoframeworks with dehydrogenase-like activity inhibit cancer proliferation effectively.

Expanding the Structural Topologies of Rare-Earth Porphyrinic Metal-Organic Frameworks through Ligand Modulation.

Expanding the structural diversity of porphyrinic metal-organic frameworks (PMOFs) is essential to develop functional materials with novel properties or enhanced performance in different applications. Herein, we establish a strategy to construct rare-earth (RE) PMOFs with unprecedented topology via rational functionalization of porphyrinic ligands. By introducing phenyl/pyridyl groups to the meso-positions of the porphyrin core, the symmetries and connectivities of the ligands are tuned, and three RE-PMOFs (BUT-224/-225/-226) with new topologies are successfully obtained. In addition, BUT-225(Co), with both the Lewis basic and acidic sites, exhibits enhanced CO2 uptake and higher catalytic activity for the cycloaddition of CO2 and epoxides under mild conditions. This work reveals that the RE-PMOFs with novel topologies can be rationally designed and constructed through ligand functionalization, which provides insights into the construction of tailored PMOFs for various applications.